Medicine:Powassan virus

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Short description: Species of pathogenic Flavivirus transmitted by ticks


Powassan virus
Virus classification e
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Kitrinoviricota
Class: Flasuviricetes
Order: Amarillovirales
Family: Flaviviridae
Genus: Flavivirus
Species:
Powassan virus
Member viruses[1]

Powassan virus (POWV) is a Flavivirus transmitted by ticks, found in North America and in the Russian Far East. It is named after the town of Powassan, Ontario, where it was identified in a young boy who eventually died from it. It can cause encephalitis, inflammation of the brain. No approved vaccine or antiviral drug exists. Prevention of tick bites is the best precaution.

Classification and occurrence

Powassan virus (POWV) is a Flavivirus named after the town of Powassan, Ontario, Canada, where it was identified in a 5-year-old boy who died from encephalitis in 1958.[2][3] The ICTV species name for the Powassan Virus is Orthoflavivirus powassanense.[4] The virus exists in North America and causes long-term neurological sequelae.[5][6][7] The first human case in the United States was found in 1970 in New Jersey and in Russia in 1978.[2] (As of 2010), Powassan virus has been noted as the only tick-borne Flavivirus in North America with human pathogenicity.[8]

Powassan virus is also found in the warm climate across Eurasia, where it is part of the tick-borne encephalitis virus-complex.[9] It is found in the Russian Far East (Primorsky Krai) and appears to have been introduced there 70 years ago.[10]

Evolution

Powassan virus is an RNA virus split into two separate lineages: Lineage I, labeled as the "prototype" lineage; and Lineage II, the deer tick virus (DTV) lineage.[9] Lineage II has the most genetic variation, which indicates that it is most likely the ancestral lineage that split as a result of positive natural selection.[9] DTV is very closely related to Powassan virus and a sequence analysis showed that the two viruses diverged about 200 years ago.[11] Even though Lineage II has been predominant in POWV positive tick pools, both lineages have had confirmed cases of human disease in North America and Russia[7][12] The lineages share 84% nucleotide sequences and 94% amino acid sequence identity.[9] Cross-neutralization occurs among flaviviruses due to the conservation of the envelope protein; this is what contributes to the fact that the two lineages are "serologically indistinguishable."[6] As a result, the lineages are part of the same viral species.[10]

According to the last data,[13] evolutionary rate of Powassan virus is 3.3 × 10−5 nucleotide substitution per site per year (95% HPD, 2.0 × 10−5–4.7 × 10−5), which is significantly lower than values reported in the previous studies.[11][14] The values is compatible with that of tick-borne encephalitis virus (TBEV) and louping-ill virus (LIV) (1.0 × 10−5–2.2 × 10−5 for TBEV[15][16] and 5.7 × 10−6–3.9 × 10−5 for LIV[17]).

The most recent common ancestor of modern POWV split into two independent genetic lineages between 2600 and 6030 years ago probably as a result of the Beringia flood about 11.72 thousand years ago.[13]

Vectors

The virus can be transmitted with bites from altogether six known species of ticks; the following four species of Ixodes ticks: Ixodes cookei, Ixodes scapularis, Ixodes marxi and Ixodes spinipalpus and the ticks Dermacentor andersoni and Dermacentor variabilis.[6]

People with POWV have been mostly confirmed as having one strain of POWV, the deer tick virus.[9] I. scapularis is an important vector for the deer tick virus, which plays a vital role in maintaining the POWV.[9] I. scapularis is also a primary vector for the agent of Lyme disease, because they are generalist feeders and readily bite humans.[7]

In Canada and the Northeastern United States Ixodes cookei is the predominant species, while I. scapularis is a significant vector in Minnesota and Wisconsin.[7] POWV is transmitted when an infected tick bites a mammal; in humans the tick is typically I. scapularis.[18] In North America, the lineages of the POWV are maintained in three main enzootic cycles[9] involving three different tick species and their respective small to medium-sized woodland mammals.[9] POWV may infect I. cookei and woodchucks, or it may infect I. marxi and squirrels, and it can cycle between I. scapularis and white-footed mice.[12]

Based on the time interval for other tick-borne diseases like Lyme disease and anaplasmosis, the time interval for transmission of POWV is expected to be less than 12 hours.[19] Once the POWV reaches humans it cannot be transmitted to a feeding tick, therefore humans are considered "dead-end" hosts.[12] (As of 2004), the fastest transmission time of DTV from a I. scapularis nymph to a mouse was no more than 15 minutes.[20]

Symptoms

Powassan virus infection is rarely diagnosed as a cause of encephalitis; however, when it is, Powassan encephalitis is severe, and neurologic sequelae are common.[6] Powassan encephalitis has symptoms compatible with acute disseminated encephalomyelitis, oftentimes making it difficult to diagnose.[6] Powassan virus encephalitis is a challenge to diagnose because there are only a few laboratories that offer testing, the most effective being serologic testing.[21]

There are currently no medications or approved vaccines to treat or prevent the POWV. People affected by Powassan virus generally first show symptoms 1 to 3 weeks after infection.[7] The initial symptoms include fever, headache, nausea, occasional confusion, and weakness.[12] With severe Powassan illnesses the victims should be hospitalized, because the symptoms do worsen. If not treated, symptoms could extend to meningoencephalitis, which may include: seizures, aphasia, cranial nerve palsies, paresis and altered mental status.[7][12] Currently, the best ways to treat POWV illnesses include medications to reduce brain swelling, respiratory support and intravenous fluids.[12] About 10% of POWV encephalitis cases are fatal and half the survivors have permanent symptoms that affect their brain.[19]

Reported cases (2001–present)

There were 33 confirmed cases of Powassan virus infection in the U.S. between 2001 and 2010.[7]

A rare case of a five-month-old Connecticut infant boy contracting Powassan virus infection was published in 2017. He survived with normal motor and verbal development on follow-up at the age of 10 months, but a head MRI showed severely abnormal brain conditions, including scarring (gliosis) and softening (encephalomalacia) in the thalamus and basal ganglia on both sides, and volume loss and early mineralization in the left basal ganglia.[22]

On October 28, 2019, former U.S. Senator Kay Hagan died after contracting Powassan virus in 2016. She was 66 years old.[23]

In May 2022, the Connecticut Department of Public Health confirmed that a man aged in his 50s contracted Powassan virus in the state during March and was hospitalised with severe neurological symptoms, though he was later discharged from hospital to recover at home.[24] In May 2023, the Maine Center for Disease Control and Prevention reported that a 58-year-old adult male from Sagadahoc County died from Powassan virus.[25]

Epidemiology

Powassan Virus (POWV) is the only tick-borne flavivirus endemic in North America.[2] POWV human illnesses have been reported in the United States, Canada and Russia.[2] POWV has different genetic variations including deer tick virus (DTV) which is transmitted by the black-legged tick (aka deer tick), Ixodes scapularis.[26] It has two distinct lineages. POWV lineage I is transmitted by the Ixodes cookei which is endemic in the Great Lakes region of the United States.[3] POWV lineage II is transmitted by Ixodes scapularis which is endemic in the Northeast United States.[3] Humans can become infected in 15 to 30 minutes after tick attachment.[3][2][27]

Ixodes ticks have three life stages that require a host: larva, nymph and adult.[28] Each stage requires a blood meal to progress to the next life stage. The nymph stage frequently bites humans and is the stage in which I. scapularis is most likely to infect a human host with a pathogen.[29] The most common reservoir (or host) for I. scapularis are white-footed mouse and white-tail deer.[3][30] The most common reservoirs for I. cookei are skunks, woodchucks and squirrels.[3] Humans are incidental hosts which means the ticks do not need to feed on humans to survive, humans are merely the host they find at the time for their next blood meal.[31]

In the US, the highest incidence of POWV is in Minnesota and Wisconsin, with Massachusetts and New York also having higher incidence than other states in the Great Lakes or Northeast region.[2] POWV was included in the list of nationally notifiable diseases to the U.S. Centers for Disease Control and Prevention (CDC) in 2002.[31] Between 2009 and 2018, 133 cases of neuroinvasive POWV and 12 cases of non-neuroinvasive POWV were reported to the CDC.[32] Since its discovery in 1958, there have only been 150 reported human illnesses caused by POWV.[2] The incidence rate of POWV in the United States was 1 case per year from 1958 to 2005, and has risen to an average of 10 cases per year since then.[2]

Currently, POWV is detected with IgM antibody capture ELISA of an IgM immunofluorescence antibody (IFA) assay, plaque reduction neutralization test (PRNT), detection of virus-specific nucleic acids, isolation in culture, or a >4-fold increase in antibody titers from paired acute and convalescent sera.[33] These specific tests for POWV can only be done at a state lab or the CDC.[2] Diagnostic criteria as set by the CDC are: resides in an endemic area, reported tick exposure, and presented with fever, altered mental status, seizures and focal neurological deficits and blood, tissue or cerebrospinal fluid (CSF) are positive on Powassan IgM or Powassan PRNT tests.[3][2]

Research

Scientists at Vaccine and Immunotherapy Center at The Wistar Institute have designed and tested the first-of-its-kind synthetic DNA vaccine candidate against Powassan virus (POWV), targeting portions of the virus envelope protein.[34][35]

References

  1. ↑ "Genus: Flavivirus" (in en). 20 March 2019. https://ictv.global/report/chapter/flaviviridae/flaviviridae/flavivirus. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 "Tick-Borne Flaviviruses, with a Focus on Powassan Virus". Clinical Microbiology Reviews 32 (1): e00106–17, /cmr/32/1/e00106–17.atom. January 2019. doi:10.1128/CMR.00106-17. PMID 30541872. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "First confirmed case of Powassan neuroinvasive disease in Rhode Island". IDCases 12: 84–87. 2018. doi:10.1016/j.idcr.2018.03.016. PMID 29942757. 
  4. ↑ "KEGG GENOME: Powassan virus". https://www.genome.jp/entry/gn:11083. 
  5. ↑ Campbell, O.; Krause, P. J. (2020). "The emergence of human Powassan virus infection in North America.". Ticks and Tick-borne Diseases 11 (6): 101540. doi:10.1016/j.ttbdis.2020.101540. PMID 32993949. https://www.sciencedirect.com/science/article/abs/pii/S1877959X20302156. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 "Powassan virus infection presenting as acute disseminated encephalomyelitis in Tennessee". The Pediatric Infectious Disease Journal 30 (1): 86–88. January 2011. doi:10.1097/INF.0b013e3181f2f492. PMID 20736878. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 "Powassan virus encephalitis, Minnesota, USA". Emerging Infectious Diseases 18 (10): 1669–1671. October 2012. doi:10.3201/eid1810.120621. PMID 23017222. 
  8. ↑ "Zoonotic tick-borne flaviviruses". Veterinary Microbiology 140 (3–4): 221–228. January 2010. doi:10.1016/j.vetmic.2009.08.024. PMID 19765917. 
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 "Homogeneity of Powassan virus populations in naturally infected Ixodes scapularis". Virology 402 (2): 366–371. July 2010. doi:10.1016/j.virol.2010.03.035. PMID 20434750. 
  10. ↑ 10.0 10.1 "[Molecular evolution of the tick-borne encephalitis and Powassan viruses]". Molekuliarnaia Biologiia 46 (1): 82–92. 2012. doi:10.1134/S0026893311060148. PMID 22642104. 
  11. ↑ 11.0 11.1 "Molecular epidemiology of Powassan virus in North America". The Journal of General Virology 91 (Pt 11): 2698–2705. November 2010. doi:10.1099/vir.0.024232-0. PMID 20631087. 
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 "Powassan". Centers for Disease Control and Prevention. 2010. https://www.cdc.gov/powassan/. 
  13. ↑ 13.0 13.1 "Phylogeography and Re-Evaluation of Evolutionary Rate of Powassan Virus Using Complete Genome Data" (in en). Biology 10 (12): 1282. 6 December 2021. doi:10.3390/biology10121282. PMID 34943197. 
  14. ↑ "[Molecular evolution of the tick-borne encephalitis and Powassan viruses]". Molekuliarnaia Biologiia 46 (1): 82–92. January 2012. PMID 22642104. 
  15. ↑ "Rate of evolution and molecular epidemiology of tick-borne encephalitis virus in Europe, including two isolations from the same focus 44 years apart". The Journal of General Virology 93 (Pt 4): 786–796. April 2012. doi:10.1099/vir.0.035766-0. PMID 22205716. 
  16. ↑ ""886-84-like" tick-borne encephalitis virus strains: Intraspecific status elucidated by comparative genomics". Ticks and Tick-Borne Diseases 10 (5): 1168–1172. August 2019. doi:10.1016/j.ttbdis.2019.06.006. PMID 31253516. 
  17. ↑ "Population genomics of louping ill virus provide new insights into the evolution of tick-borne flaviviruses". PLOS Neglected Tropical Diseases 14 (9): e0008133. September 2020. doi:10.1371/journal.pntd.0008133. PMID 32925939. 
  18. ↑ "Update on Powassan virus: emergence of a North American tick-borne flavivirus". Annual Review of Entomology 55 (1): 95–110. 11 August 2009. doi:10.1146/annurev-ento-112408-085446. PMID 19961325. 
  19. ↑ 19.0 19.1 "Minnesota Department of Health". Powassan. MDH. http://www.health.state.mn.us/divs/idepc/diseases/powassan/basics.html. 
  20. ↑ "Short report: duration of tick attachment required for transmission of powassan virus by deer ticks". The American Journal of Tropical Medicine and Hygiene 71 (3): 268–271. September 2004. doi:10.4269/ajtmh.2004.71.3.0700268. PMID 15381804. 
  21. ↑ "Powassan virus encephalitis, Minnesota, USA". Emerging Infectious Diseases 19 (4): 686. April 2013. doi:10.3201/eid1904.121651. PMID 23750562. 
  22. ↑ "Notes from the Field: Powassan Virus Disease in an Infant - Connecticut, 2016". MMWR. Morbidity and Mortality Weekly Report 66 (15): 408–409. April 2017. doi:10.15585/mmwr.mm6615a3. PMID 28426641. 
  23. ↑ "Former US Senator Kay Hagan dead at 66 after three-year battle with encephalitis". The News & Observer. 28 October 2019. https://amp.newsobserver.com/news/politics-government/article236736088.html. 
  24. ↑ "Health Officials Urge Protection Against Tick Bites After 1st Case of Powassan Virus in CT in 2022". May 4, 2022. https://www.nbcnewyork.com/news/national-international/health-officials-urge-protection-against-tick-bites-after-first-case-of-powassan-virus-in-ct-this-year/3674034/. 
  25. ↑ Curwin, Eli (May 22, 2023). "Maine man dies from tick-borne illness". https://www.boston.com/news/local-news/2023/05/22/maine-man-dies-from-tick-borne-illness-powassan-virus-disease/. Retrieved May 22, 2023. 
  26. ↑ "Prevalence and Genetic Characterization of Deer Tick Virus (Powassan Virus, Lineage II) in Ixodes scapularis Ticks Collected in Maine". The American Journal of Tropical Medicine and Hygiene 101 (2): 467–471. August 2019. doi:10.4269/ajtmh.19-0281. PMID 31218999. 
  27. ↑ "Pathogen transmission in relation to duration of attachment by Ixodes scapularis ticks". Ticks and Tick-Borne Diseases 9 (3): 535–542. March 2018. doi:10.1016/j.ttbdis.2018.01.002. PMID 29398603. 
  28. ↑ "Emerging Tick-Borne Viruses in the Twenty-First Century". Frontiers in Cellular and Infection Microbiology 7: 298. 2017-07-11. doi:10.3389/fcimb.2017.00298. PMID 28744449. 
  29. ↑ "Prevalence and distribution of seven human pathogens in host-seeking Ixodes scapularis (Acari: Ixodidae) nymphs in Minnesota, USA". Ticks and Tick-Borne Diseases 9 (6): 1499–1507. September 2018. doi:10.1016/j.ttbdis.2018.07.009. PMID 30055987. 
  30. ↑ "Integrated control of juvenile Ixodes scapularis parasitizing Peromyscus leucopus in residential settings in Connecticut, United States". Ticks and Tick-Borne Diseases 9 (5): 1310–1316. July 2018. doi:10.1016/j.ttbdis.2018.05.014. PMID 29859885. 
  31. ↑ 31.0 31.1 "The Blacklegged Tick, Ixodes scapularis: An Increasing Public Health Concern". Trends in Parasitology 34 (4): 295–309. April 2018. doi:10.1016/j.pt.2017.12.006. PMID 29336985. 
  32. ↑ "Statistics & Maps | Powassan". Centers for Disease Control and Prevention. 2019-07-10. https://www.cdc.gov/powassan/statistics.html. 
  33. ↑ "Serologic Evidence of Powassan Virus Infection in Patients with Suspected Lyme Disease1". Emerging Infectious Diseases 23 (8): 1384–1388. August 2017. doi:10.3201/eid2308.161971. PMID 28726610. 
  34. ↑ "New synthetic DNA vaccine against Powassan virus: Vaccine protects animals against tick-borne Powassan virus, an emerging infectious disease". https://www.sciencedaily.com/releases/2020/10/201030122534.htm. 
  35. ↑ "A novel synthetic DNA vaccine elicits protective immune responses against Powassan virus". PLOS Neglected Tropical Diseases 14 (10): e0008788. October 2020. doi:10.1371/journal.pntd.0008788. PMID 33119599. 

External links

Wikidata ☰ Q3053946 entry



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